Biosemiotic Entropy of the Genome: Mutations and Epigenetic Imbalances Resulting in Cancer

Abstract

Biosemiotic entropy involves the deterioration of biological sign systems. The genome is a coded sign system that is connected to phenotypic outputs through the interpretive functions of the tRNA/ribosome machinery. This symbolic sign system (semiosis) at the core of all biology has been termed "biosemiosis". Layers of biosemiosis and cellular information management are analogous in varying degrees to the semiotics of computer programming, spoken, and written human languages. Biosemiotic entropy-an error or deviation from a healthy state-results from errors in copying functional information (mutations) and errors in the appropriate context or quantity of gene expression (epigenetic imbalance). The concept of biosemiotic entropy is a deeply imbedded assumption in the study of cancer biology. Cells have a homeostatic, preprogrammed, ideal or healthy state that is rooted in genomics, strictly orchestrated by epigenetic regulation, and maintained by DNA repair mechanisms. Cancer is an eminent illustration of biosemiotic entropy, in which the corrosion of genetic information via substitutions, deletions, insertions, fusions, and aberrant regulation results in malignant phenotypes. However, little attention has been given to explicitly outlining the paradigm of biosemiotic entropy in the context of cancer. Herein we distill semiotic theory (from the familiar and well understood spheres of human language and computer code) to draw analogies useful for understanding the operation of biological semiosis at the genetic level. OPEN ACCESSEntropy 2013, 15 235We propose that the myriad checkpoints, error correcting mechanisms, and immunities are all systems whose primary role is to defend against the constant pressure of biosemiotic entropy, which malignancy must shut down in order to achieve advanced stages. In lieu of the narrower tumor suppressor/oncogene model, characterization of oncogenesis into the biosemiotic framework of sign, index, or object entropy may allow for more effective explanatory hypotheses for cancer diagnosis, with consequence in improving profiling and bettering therapeutic outcomes.

Biological Water Dynamics and Entropy: A Biophysical Origin of Cancer and Other Diseases

“…Our thesis differs substantively from that of Gryder, Nelson, and Shepard [349], in positing that structured interfacial water orchestrates all of the highly-stereotyped biophysical processes underlying life. Whereas Gryder et al applied the central dogma, the SMT, to Oller's biosemiotic entropy hypothesis [1], our EIWS thesis is supportive and furthers the TOFT, which, as expressed by Sonnenschein and Soto, removes the gene from the driver's seat (genetic determinism) and introduces the organism and its ability to self-organize as the conceptual focus (organicism) of the biology of cancer [293,295,350].…”

Histone Deacetylase Inhibitors Equipped with Estrogen Receptor Modulation Activity

“…Aberrant HDAC activity can result in epigenetic imbalance 3 and has been linked to cell proliferation in many cancers. 1–3 In particular, over-expression of HDAC1, HDAC6, and HDAC8 has been linked to breast tumors. 4 As a result, the use of HDAC inhibitors (HDACi) as cancer therapeutics is an area of active investigation.…”

Biosemiotic Entropy: Concluding the Series

“…As strings are made less coherent (more degenerate), the approximations become measurably more difficult to process [22,24]. Evidently, based on empirical studies, genetic polymers also appear to be resistant to distortion, or even complete erasure in some cases, thus displaying a similar kind of pragmatic redundancy as is found in linguistic discourse-e.g., see Gryder, Nelson, and Shepard regarding the error correcting powers of genetic systems [8]. Error correction, however, depends entirely on making a string of signs agree with some underlying meaning or some model string, and thus with some system of facts known through TNRs.…”

“…This series has explored some of the ways factors known to increase biosemiotic entropy tend to cause disorders, diseases, and mortality. One of the most persuasive and perspicuous applications of TNR theory in the series is the article by Gryder, Nelson, and Shepard [8] regarding the etiology of cancers (also see [9]). Given the fact that agreement between distinct physical manifestations of representations is important to the attainment of any coherence in any representational system of any kind, it follows that the traditional concepts of physics concerning the nature of entropy are bound to be applicable to such physical manifestations of information systems in general.…”

“…It is the purpose of this paper to show why this result flows necessarily from the nature of what contributors to this special issue have called biosemiotic entropy. At any rate, the prediction of universal mortality is certain and inviolable at the organismic level, and for reasons spelled out in contributions by Davidson and Seneff [2], the Dieterts [4], Gryder et al [8], Samsel and Seneff [11], and Ho [13], it appears that irreversible biosemiotic entropy in the human genome is on an accelerating course toward mortality on a grander scale. …”